The present invention relates to electroactive carbazole polymers and particularly cationic drug release from such polymers.
Electrochemical methods of drug release have been attempted with the goal of precisely controlling the delivery rate by application of threshold potentials and current flow. In this area of medication an electrically conducting polymer, such as polypyrrole or polythiophene, is usually prepared through electrochemical oxidation to form the oxidized polymer and is electrochemically reduced with a resultant release of a negatively charged counterion which counterion has drug effects.
A drug so released is described in the article by Blankespoor et al in J. Chem. Soc., Chem. Commun., 90 (1985), relative to the release of the glutamate anion which is important in neurotransmission. However, the number of negatively charged drug molecules is quite small in comparison to the number of cationic alkylammonium based drugs which exert powerful effects on the central nervous system. One attempt to achieve cation-specific release involved the use of a polypyrrole/polystyrene sulfonate molecular composite film which was deposited on an electrode by electropolymerizing and oxidizing pyrrole in the presence of the polystyrene sulfonate anion (Miller et al., Macromol., 20,1594 (1987)). This system contained an immobilized dopant anion (polystyrene sulfonate), thus electrochemical reduction of the polymer in the presence of dopamine resulted in adsorption of the drug cation into the polymer film to compensate for the positive charge that had been removed from the polymer chain. The medication could be rereleased by reoxidation of the conducting polymer.
So called, "self-doped", N-alkane sulfonate substituted pyrrole copolymers have become available (Reynolds et al., J. Chem. Soc., Chem. Comm., 620 (1987)) along with 3-alkyl substituted thiophene conducting polymers (Pastil et al., JACS, 109, 1858 (1987)). With these materials, the mechanism of mobile countercation release involves electrochemical oxidation of the polymer backbone to produce a charge compensated polymeric zwitterion. However, once the pyrrole is alkane sulfonated at the nitrogen position steric disturbances force loss of ring planarity and loss of conduction requiring the copolymerization with unsubstituted pyrrole monomer. This acts to limit the total loading of cationic drugs onto the conducting polymer matrix. Thus, for example, polythiophene 3-substituted alkane sulfonates do not have the steric interference problems of the N-substituted pyrroles but do have air and water stability problems.